Year three, Pathology: Blood vessel diseases:
Lecture 4: Vasculitis:
February 2018 by Dr. Ehsan.
Vasculitis is Inflammation, often with necrosis of blood vessels.
It is of diverse clinical setting. Can be arteritis, vasculitis, angiitis are used because in addition to arteries and arterioles, veins and capillaries may be involved.
The two common pathogenic mechanismsof vascular injury can be of:
Immune-mediated inflammation and,
Direct invasion of vascular walls by infectious pathogens.
Infections can indirectly induce immune mediated damage through either the formation of immune complexes or triggering cross reactivity.
Examples of infectious vasculitis:
Bacterial (Neisseria)
Spirochetal (syphilis)
Fungal (aspergillosis, mucomycosis)
Viral (herpes zoster)
Physical and chemical injury, such as from irradiation, mechanical trauma, and toxins, can also cause vasculitis.
It is important to distinguish between direct infections & immune mechanism, because immunosuppressive therapy is the appropriate treatment for the latter that would be harmful for infectious vasculitis (suppressing immunity may→ flare up of infection).
Non infectious Vasculitis:
The major cause of noninfectious vasculitis is a local or systemic immune response Immunologic injury in noninfectious vasculitis may be caused by::
Immune complex associated vasculitis.
Antineutrophil cytoplasmic antibodies.
Antiendothelial cell antibodies.
Autoreactive T cells
Immune Complex-Associated Vasculitis
This form of vasculitis can be seen in systemic immunologic disorders such as systemic lupus erythematosus that are associated with autoantibody production and formation of immune complexes that deposit in vessels.
Immune complex deposition is also implicated in the following vasculitides:
Drug hypersensitivity vasculitis.
Vasculitis secondary to infections.
Antineutrophil Cytoplasmic Antibodies:
Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens, so-called antineutrophil cytoplasmic antibodies (ANCAs). For example Anti-proteinase-3 & Anti-myeloperoxidase.
Classification of vasculitis:
It depends on the size of the vessel involved, anatomic site, histological features and the clinical manifestations so divided into:Large vessel Vasculitis, as giant cell arteritis.
Medium sized vessel Vasculitis, as polyarteritis nodosa and Kawasaki disease.
Small vessel Vasculitis, as Wegner granulomatosis.
Giant cell (temporal) arteritis:
It is the most common form of vasculitis among elderly in US and Europe.
It is characterized by a chronic, granulomatous, inflammation of large to small arteries. It involves principally arteries in the head especially the temporal arteries in patient over 50 years.
Other arteries may be involved are vertebral and ophthalmic arteries. The aortic arch also can be involved (giant cell aortitis).
Pathogenesis:
Most evidence suggests that giant cell arteritis arises from a T-cell–mediated immune response against one of vessel wall antigens.
So there is cellular immune response evident by the characteristic granulomatous
response.
Clinical features:
There is severe throbbing pain & tenderness over the involved temporal artery, associated with swelling and redness of the overlying skin. Often there is claudication of the jaw and blurring of vision, diplopia or sudden blindness.
Biopsy of the temporal artery is required to confirm the clinical diagnosis.
Microscopy:
There is nodular intimal thickening (with occassional thrombosis) that leads to reduction in luminal diameter, medial granulomatous inflammation and end with elastic lamina fragmentation.
Also there is infiltrate of lymphocytes, macrophages, and multinucleated giant cells.
Polyarteritis nodosa:
It is a systemic vasculitis of small- or medium-sized muscular arteries, typically
involving renal and visceral vessels but sparing the pulmonary circulation.
Gross pathology:
Classic polyarteritis nodosa is characterized by segmental transmural necrotizing inflammation of small- to medium sized arteries.
Vessels of the kidneys, heart, liver, and gastrointestinal tract are involved in descending order of frequency.
Lesions usually involve only part of the vessel circumference. The inflammatory process weakens the arterial wall and can lead to aneurysms or even rupture. Can result in ulcerations, infarcts, ischemic atrophy, or hemorrhages.
There is sharply localized segmental transmural involvement of the artery.
Microscopically:
During the acute phase there is transmural inflammation of the arterial wall with a mixed infiltrate of neutrophils, eosinophils, and mononuclear cells, frequently accompanied by fibrinoid necrosis. Luminal thrombosis can occur.
Later, the acute inflammatory infiltrate is replaced by fibrous thickening of the vessel wall that can extend into the adventitia.
All stages can be seen at the same time in the same vessel.
Clinical Features.
Although typically a disease of young adults, PAN can also occur in pediatric and geriatric populations.
Clinical manifestations result from ischemia and infarction of affected tissues and organs.
The course is frequently remitting and episodic, with long symptom-free intervals. The usual presentation can involve some combination of rapidly accelerating hypertension due to renal artery involvement; abdominal pain and bloody stools
caused by vascular gastrointestinal lesions; diffuse myalgias; and peripheral neuritis, predominantly affecting motor nerves.
The renal involvement is often prominent and is regarded as the major cause of mortality.
Untreated, PAN is typically fatal; however, immunosuppression can yield remissions or cures in 90% of cases.
Kawasaki disease: (Mucocutaneous lymph node Syndrome)
It is an acute systemic febrile disorder of infancy and childhood and is usually self limited and is characterized by:
Skin rash .
Erythema of the conjunctivae, oral mucosa, palms and feet.
Cervical lymphadenopathy.
Vasculitis that involves the coronaries and resemble PAN.
Death occurs due to coronary arteritis and thrombosis or rupture of coronary artery aneurysm.
Cause: is unknown but a variety of infectious agents (mostly viral) have been implicated in triggering the disease in genetically susceptible individuals. T cell and macrophage activation (presumably to a virus) results in the formation of autoantibodies to the endothelial cells.
Thromboangiitis Obliterans (Burger's disease):
It is a segmental vasculitis with thrombosis of medium sized and small arteries principally tibial and radial arteries and sometimes veins of the extremities.
It is almost exclusively occurring in young men who are heavy cigarette smokers.
It is characterized by endothelial injury directly or by hypersensitivity to tobacco products.
Clinically:
There are features of vascular insufficiency e.g. pain on exercise and intermittent claudication.
It can be complicated by gangrene of the extremities & amputation.
Remission and relapses correlate with cessation and resumption of smoking.
Summary:
Vasculitis- Vasculitis is defined as inflammation of vessel walls; it is frequently associated with systemic manifestations (including fever, malaise, myalgias, and arthralgias) and organ dysfunction that depends on the pattern of vascular involvement.
- Vasculitis can result from infections, but more commonly has an immunologic basis, including immune complex deposition, formation of anti-neutrophil antibodies (ANCA), or T cell responses to vascular wall antigens.
- Different forms of vasculitis tend to specifically affect vessels of a particular caliber and location, and the clinical manifestations depend on the pattern of vessel involvement.
Disorders of blood vessels hyperreactivity:
Raynaud's phenomenon (primary):
It is characterized by attacks of pallor or cyanosis of the fingers or toes caused by intense vasospasm of local small arteries or arterioles.
This results in changes in color of fingers and toes through the sequence of red-white –blue from proximal to distal.
The disease is seen in healthy young females.
The arterial and arteriolar walls are devoid of structural changes.
It is of unknown cause, & it is a reflection of exaggerated normal vasomotor response to cold or emotion.
Secondary Raynaud phenomenon:
It refers to vascular insufficiency due to arterial disease caused by other disease entities.
Classification of Vascular Tumors and Tumor-Like Conditions:
Benign Neoplasms, Developmental and Acquired ConditionsHemangioma
Capillary hemangioma
Cavernous hemangioma
Pyogenic granuloma
Lymphangioma
Simple (capillary) lymphangioma
Cavernous lymphangioma (cystic hygroma)
Glomus tumor
Vascular ectasias
As telangiectasis
Reactive vascular proliferations
Bacillary angiomatosis
Intermediate-Grade Neoplasms
Kaposi sarcoma
Hemangioendothelioma
Malignant Neoplasm
Angiosarcoma
Hemangiopericytoma
Summary:
Vascular Tumors
Vascular ectasias are not neoplasms, but rather dilations of existing vessels.
Vessel neoplasms can derive from either blood vessels or lymphatics, and can be composed of endothelial cells (hemangioma, lymphangioma, angiosarcoma) or other components of vascular wall cells
Most vascular tumors are benign (e.g., hemangiomas), some have an intermediate, locally aggressive behavior (e.g., Kaposi sarcoma), and others are highly malignant (e.g., angiosarcoma).
Benign tumors typically form obvious vascular channels lined by normal appearing endothelial cells. Malignant tumors are more often solid and cellular, exhibit cytologic atypia, and lack well-defined vessels.
Pathology of Vascular Interventions:
The morphologic changes that occur in vessels after therapeutic intervention—balloon angioplasty, stenting, or bypass surgery— are similar to many of the changes that occur in the setting of any vascular insult.ANGIOPLASTY AND ENDOVASCULAR STENTS
Balloon angioplasty (dilation of a stenotic artery by inserting an intravascular catheter), with or without endovascular stenting, is used extensively to restore flow at sites of focal vascular stenosis—especially in the coronary circulation (percutaneous transluminal coronary angioplasty).
Simple balloon dilation (without stenting) of an atherosclerotic vessel:
Mechanism: induces medial stretching and causes plaque fracture, often with accompanying localized hemorrhagic dissection of the adjacent arterial wall; in this manner vascular flow is restored, with risks of more extensive dissection and luminal thrombosis (to prevent the latter, anticoagulation is required for a period of time after the procedure). Most patients improve symptomatically, at least in the short term.
Complications:
Abrupt reclosure may occur as a result of compression of the lumen by an extensive circumferential or longitudinal dissection or by thrombosis.
The long-term success of angioplasty is primarily limited by the development of proliferative restenosis, due to intimal thickening; this occurs in approximately 30% to 50% of patients within the first 4 to 6 months after the procedure. Occur in response to mechanical vascular injury with thrombosis. The end result is an occlusive, progressive fibrous lesion that contains abundant smooth muscle cells and extracellular matrix.
Coronary stents are expandable tubes of metallic mesh that are inserted to preserve lumenal patency during angioplasty; they are now used in over 90% of angioplasty procedures.
Mechanism: Causing focal plaque erosion and/or endothelial cell disruption, cause acute thrombosis, and a successful procedure also requires at least transient anticoagulation with potent anti-thrombotic agents (platelet antagonists).
A late complication of bare metal stents involves proliferative intimal thickening leading to proliferative restenosis much like that seen with percutaneous transluminal coronary angioplasty alone.
The newest generation of stents are coated with anti-proliferative drugs (e.g., paclitaxel or rapamycin) that limit smooth muscle cell hyperplasia; this results in markedly diminished intimal thickening.
VASCULAR REPLACEMENT
Synthetic or autologous vascular grafts are increasingly used to replace damaged vessels or bypass diseased arteries.
Small-diameter artificial grafts (≤8 mm in diameter) generally fail because of early thrombosis or late intimal hyperplasia, primarily at the junction of the graft with the native vasculature
Consequently, where small-bore vessels are needed e.g., for coronary artery bypass, grafts are most commonly composed of either reversed autologous saphenous vein (taken from the patient's own leg) or left internal mammary artery (because of its proximity to the heart).
The long-term patency of saphenous vein grafts is only 50% at 10 years; grafts occlude because of thrombosis (typically early), intimal thickening (months to years postoperatively), and vein graft atherosclerosis—sometimes with superimposed plaque rupture, thrombi, or aneurysms (usually >2–3 years). In contrast, greater than 90% of internal mammary artery grafts are patent at 10 years.